Certain azapirones, such as the compounds of Formula II, have been shown to have therapeutic potential when hydroxylated to form hydroxyazapirones of Formula I. Two examples of hydroxyazapirones are 6-hydroxybuspirone (R1 and R2 are 1,4-butandiyl and n is 4) and 3-hydroxygepirone (R1 and R2 are methyl and n is 4). Initially discovered as metabolites (see Mayol et al. Clin. Pharmacol. Ther. 1985 37, 210 and Kerns et al. J. Pharmaceut and Biomedical Analysis 1999 20, 115-128), these compounds are now believed to be biologically active and their use in treating anxiety disorders and depression has been disclosed (Mayol, R. F. U.S. Pat. No. 6,150,365, 2000; Rider, P. H. PCT appl. WO 02/16347, 2002). As these compounds show promise in therapy, improved methods for their production would be of benefit. 
Processes which selectively hydroxylate Formula II azapirones into Formula I hydroxyazapirones have been disclosed (Mayol, R. F. U.S. Pat. No. 6,150,365, 2000; Rider, P. H. PCT appl. WO 02/16347, 2002). One process for hydroxylating both buspirone and gepirone is illustrated in Scheme 1. In this process, the imide enolate derived from imide II was generated and trapped by di-4-nitrobenzyl peroxydicarbonate [(PNBOCO)2] to produce intermediate X. After chromatographic purification, hydrogenation of intermediate X afforded the Formula I compound. 
A second process, shown in scheme 2, was employed for buspirone hydroxylation. In this process, the imide enolate derived from II was reacted with 2-(phenylsulfonyl)-3-phenyloxaziridine (the Davis reagent) to form the postulated intermediate V. Acidic workup provided the Formula I product.
Drawbacks of both these processes include the requirement to synthesize the starting reagents and the necessity of chromatographically purifiying the products. 
A third process involving enzymatic conversion in certain mammalian liver microsomes was not amenable to large-scale synthesis.
By contrast, the invention disclosed below improves upon these processes by employing a one step procedure using commercially available reagents and air. The process also provides direct crystallization of the product rather than chromatographic purification.